Plizil

General characteristics. Structure:

Active ingredient of a paroksetin мезилат 25,83 mg, in terms of пароксетин 20 mg;
excipients: calcium hydrophosphate anhydrous, carboxymethylstarch of sodium, magnesium stearate; film cover: lactose monohydrate, gipromelloz, titanium dioxide (Е 171), macrogoal 4000, ferrous oxide yellow (Е 172), ferrous oxide red (Е 172).

Description: round tablets, film coated, from yellow till orange color, with an engraving of "POT 20" on one party and risky on both parties.

Pharmacological properties:

Paroksetin is powerful and selection inhibitor of capture of a 5-gidroksitriptamin (5-HT, serotonin) brain neurons that defines its antidepressive action and efficiency at treatment of obsessivno-compulsive (ROC) and panic frustration.

The main metabolites of a paroksetin represent the polar and conjugated products of oxidation and methylation which are quickly brought out of an organism, have weak pharmacological activity and do not influence its therapeutic action. At metabolism of a paroksetin the selection capture caused by its action is not broken by 5-HT neurons.

Paroksetin has low affinity to muskarinovy cholinergic receptors.

Possessing the selection action, in difference from tricyclic antidepressants, пароксетин showed low affinity to a-1, a-2, b-adrenoceptors, and also to dopamine, 5-HT1 similar, 5-HT2 similar and histamine (H1) receptors. Paroksetin does not break psychomotor functions and does not potentsiirut oppressing effect of ethanol on them.

According to a research of behavior and EEG, at a paroksetin the weak activating properties when it is appointed in doses come to light is higher than those which are necessary for inhibition of capture 5-HT. It does not cause considerable change of level of arterial pressure, heart rate and EEG in healthy volunteers.

Unlike antidepressants which inhibit capture of noradrenaline пароксетин suppresses anti-hypertensive effects of a guanetidin much more weakly.

Pharmacokinetics. Paroksetin is well soaked up after intake and is exposed to metabolism of the first passing through a liver. Allocation of not changed paroksetin with urine usually makes less than 2% of a dose, and metabolites make about 64% of a dose. Intestines excrete about 36% of a dose probably through bile in which not changed пароксетин makes less than 1% of a dose. Thus, пароксетин it is removed preferential in the form of metabolites.

Removal from an organism of metabolites of a paroksetin bi-phase, at first as a result of metabolism of the first passing through a liver, and then it is controlled by system elimination. The elimination half-life varies, but usually makes about 16-21 hour

Equilibrium concentration is reached by 7-14 day after an initiation of treatment, and the pharmacokinetics during prolonged treatment does not change. Clinical effects of a paroksetin (side effect and efficiency) do not correlate with its concentration in plasma.

As metabolism of a paroksetin includes a stage of the first passing through a liver, its quantity defined in system circulation is less than that which is absorbed from zheludochno - an intestinal path. At increase in a dose of a paroksetin or at repeated dosing when load of an organism increases, there is a partial absorption of effect of the first passing through a liver and decrease in plasma clearance of a paroksetin. As a result of it increase in concentration of a paroksetin in plasma and fluctuations of pharmacokinetic parameters is possible that can be observed only at those patients who at reception of low doses reach low levels of drug in plasma.

Paroksetin is extensively distributed in fabrics, and pharmacokinetic calculations show that only 1 his % is present at plasma, and in therapeutic concentration of 95% is connected with proteins of plasma.

Indications to use:

- a depression of all types, including the situational, heavy endogenous depression and a depression which is followed by alarm;
- obsessivno-compulsive frustration (OCF);
- panic frustration, including with an agoraphobia;
- social alarming frustration / social phobia;
- generalized alarming frustration;
- posttraumatic stressful frustration.

Route of administration and doses:

Inside, 1 time a day, in the morning, during food. The tablet is swallowed entirely, washing down with water. The dose is selected individually within the first two-three weeks after the beginning of therapy and afterwards if necessary is adjusted.

At depressions - 20 mg of 1 times a day. In case of need the dose is gradually increased by 10 mg/days, as much as possible to 50 mg/days depending on reaction of the patient

At obsessivno-compulsive frustration an initial therapeutic dose - 20 mg/days with the subsequent weekly increase by 10 mg. The recommended average therapeutic dose - 40 mg/days, if necessary a dose can be increased to 60 mg/days.

At panic frustration an initial dose - 10 mg/days (for decrease in possible risk of development of an aggravation of panic symptomatology), with the subsequent weekly increase by 10 mg. An average therapeutic dose - 40 mg/days. The maximum dose - 50 mg/days.

Social and alarming frustration / sociophobia: the initial dose makes 20 mg a day, in the absence of effect within at least two weeks increase in a dose as much as possible to 50 mg a day is possible. It is necessary to increase a dose by 10 bucketed mg not less than a week according to clinical effect.

Posttraumatic disturbances of mentality: for most of patients initial and therapeutic doses make 20 mg a day. Increase in a dose of a paroksetin as much as possible to 50 mg a day is in certain cases recommended. The dose should be increased by 10 mg every week according to clinical effect.

Generalized alarming frustration: the initial and recommended doses - 20 mg a day.

At a renal and/or liver failure the recommended dose makes 20 mg a day.

As well as at treatment by all other antidepressants the dose of drug has to be estimated and if necessary be adjusted within two-three weeks at the beginning of therapy, and then as required. Patients have to continue treatment during the period sufficient for disappearance of symptoms, at least 4-6 months after recovery at a depression and more in the presence of obsessivno-compulsive and panic frustration. As well as for many other psychotropic drugs it is not recommended to drug withdrawal sharp.

For elderly patients the daily dose should not exceed 40 mg.

For the prevention of development of a withdrawal the termination of administration of drug is carried out gradually.

Use of a paroksetin for children is not recommended as its safety and efficiency in this population are not established.

Features of use:

In order to avoid development of a malignant antipsychotic syndrome with care appoint to the patients accepting neuroleptics.

Paroksetin does not worsen cognitive and psychomotor functions, nevertheless, as well as at treatment by other psychotropic drugs, patients have to be careful when driving and moving mechanisms.

During treatment it is necessary to abstain from alcohol intake and from occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Treatment paroksetiny is appointed 2 weeks later after cancellation of MAO inhibitors.

At patients of advanced age the hyponatremia is possible.

In certain cases it is required to dose adjustment of insulin and/or oral hypoglycemic drugs.

At development of spasms treatment paroksetiny is stopped.

At the first symptoms of a mania it is necessary to cancel therapy paroksetiny.

Within the first several weeks it is necessary to watch carefully a condition of the patient in connection with possible suicide attempts as at this time therapeutic action of a paroksetin can be still not reached.

Side effects:

From a nervous system: drowsiness, a tremor, an adynamy, sleeplessness, dizziness, fatigue, spasms, extrapyramidal frustration, hallucinations, a mania, confusion of consciousness, agitation, uneasiness, depersonalization, panic attacks, nervousness, paresthesias, decline in the ability to concentration of attention, a serotoninovy syndrome

From a musculoskeletal system: arthralgia, mialgiya, myopathy, myasthenia

From sense bodys: vision disorders, taste change

From urinogenital system: disturbances of sexual function, including impotence and frustration of an ejaculation, decrease in a libido, an anorgazmiya, an ischuria, increase of an urination.

From the alimentary system: a loss of appetite, nausea, vomiting, dryness in a mouth, locks or diarrhea, seldom or never - hepatitis.

From cardiovascular system: orthostatic hypotension.

Others: the increased sweating, allergic reactions (rash, urticaria, ekhimatoza, an itch, a Quincke's disease), a hyponatremia, disturbance of secretion of antidiuretic hormone, гиперпролактинемия / a galactorrhoea, a withdrawal at sharp drug withdrawal.

Interaction with other medicines:

Meal and antiacid means does not influence absorption and pharmacokinetic parameters of drug.

Paroksetin is incompatible with MAO inhibitors, thioridazine.

At co-administration with paroksetiny concentration of a protsiklidin increases.

During therapy paroksetiny it is necessary to abstain from alcohol intake in connection with possible strengthening of toxic effect of alcohol.

Metabolism and pharmacokinetics of a paroksetin can change at joint appointment with drugs as inductors/inhibitors of enzymes of a liver.

In communication by inhibition paroksetiny P450 cytochrome strengthening of effect of barbiturates, Phenytoinum, indirect anticoagulants, tricyclic antidepressants (нортриптилин, amitriptyline, Imipraminum, desipramine and fluoxetine), fenotiazinovy neuroleptics (thioridazine) and class 1C antiaritmik (including пропафенон), a metoprolola and increase in risk of development of side effects at co-administration of these medicines is possible.

At co-administration with the drugs inhibiting liver enzymes the dose decline of a paroksetin can be required.

Paroksetin increases a bleeding time against the background of warfarin reception, at an invariable prothrombin time.

At co-administration of a paroksetin it is recommended to be careful with atypical antipsychotic means, fenotiazina, tricyclic antidepressants, aspirin, non-steroidal anti-inflammatory drugs in connection with possible disturbances of coagulability of blood.

Co-administration with serotonergic drugs (трамадол, суматриптан) can lead to strengthening of serotonergic effect.

As well as at purpose of other selective serotonin reuptake inhibitors mutual strengthening of effect of tryptophane, drugs of lithium and a paroksetin is noted. Joint reception with drugs of lithium is carried out under control of their concentration to blood.

Joint appointment with the drugs containing tryptophane is not recommended.

At use of a paroksetin with neuroleptics, as well as other selective serotonin reuptake inhibitors, development of a malignant antipsychotic syndrome is possible.

At co-administration of a paroksetin with Phenytoinum and other antikonvulsant decrease in concentration of a paroksetin in plasma and increase in frequency of side effects is possible.

Contraindications:

- hypersensitivity to drug components;
- a concomitant use with MAO inhibitors and within 14 days after their cancellation;
- pregnancy and period of a lactation
- children and teenagers aged up to 18 years (efficiency and safety is not established).

With care: liver failure; renal failure; closed-angle glaucoma; prostate hyperplasia; mania; heart pathology; epilepsy, at unstable epilepsy it is necessary to avoid administration of drug; convulsive states; purpose of a countershock; administration of drugs, increasing risk of bleeding; existence of risk factors of the raised bleeding, the diseases increasing risk of bleeding, advanced age.

Overdose:

Symptoms: nausea, vomiting, a tremor, dryness in a mouth, mydriatic pupils, fever, changes of arterial pressure, a headache, involuntary muscular contractions, agitation, uneasiness, sinus tachycardia, perspiration, drowsiness, a nystagmus, bradycardia, a nodal rhythm

Seldom or never, at a concomitant use with other psychotropic drugs and/or alcohol changes on the electrocardiogram, a coma are possible.

Treatment: gastric lavage, absorbent carbon. If necessary - symptomatic therapy. There is no specific antidote.

Storage conditions:

At a temperature not above 30 °C. To store in the place, unavailable to children.
Period of validity: 3 years. Not to apply after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated.
On 10 tablets in the blister from PVH/PE/PVDH/of aluminum foil. On 3 blisters together with the application instruction in a cardboard pack.